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丙烯酰胺对小鼠成体神经发生及增殖相关基因的影响
张亚妹1, 王久涛1, 宋玲珍,等1
西北农林科技大学 动物医学院
摘要:
【目的】探讨丙烯酰胺对成年小鼠海马成体神经发生及增殖相关基因的影响,为了解丙烯酰胺的毒性机理提供参考。【方法】将20只10周龄雄性成年昆白小鼠(体质量(30±2) g/只),随机均分为丙烯酰胺染毒组和生理盐水对照组,丙烯酰胺染毒组通过腹腔注射丙烯酰胺进行染毒,注射剂量为50 mg/kg,连续注射14 d,第15天注射5 溴脱氧尿嘧啶核苷(BrdU,50 mg/kg,2次/d,共3 d),观察2组小鼠体质量及行为活动的变化。用BrdU标记和免疫组织化学染色方法分析丙烯酰胺染毒对小鼠齿状回神经干细胞数量的影响,用RT-PCR法研究丙烯酰胺对小鼠海马增殖相关基因JNK3、Akt1、Gsk-3βRhoARac1 mRNA表达的影响。【结果】丙烯酰胺染毒组小鼠体质量极显著低于对照组,精神萎靡、后肢无力,走路时后肢偶成劈叉姿势;与对照组相比,丙烯酰胺染毒组小鼠齿状回亚颗粒细胞层中的BrdU阳性细胞数量极显著降低(P<0.01),海马组织中JNK3和Rac1的mRNA表达量显著升高(P<0.05),Akt1、Gsk-3βRhoA的mRNA表达量极显著升高(P<0.01)。【结论】丙烯酰胺中毒能显著抑制小鼠齿状-回中成体-神经干细胞增殖,可使海马组织中增殖相关基因JNK3、Akt1、Gsk-3βRac1和RhoA的表达量发生明显变化。
关键词:  丙烯酰胺中毒  成体神经发生  免疫组织化学  增殖相关基因
DOI:
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基金项目:西北农林科技大学人才引进专项基金项目(Z-111021101)
Influence of acrylamide on adult neurogenesis and expression of proliferation associated genes of mouse
ZHANG Yamei,WANG Jiutao,SONG Lingzhen,et al
Abstract:
【Objective】This study investigated the influence of acrylamide poisoning on adult neurogenesis and expression of proliferation associated genes in hippocampus of mouse.【Method】Twenty 10-week old male adult Kunbai mice with body weight of (30±2) g were randomly divided into control group and acrylamide exposure group.Acrylamide exposure group were exposed to acrylamide by intraperitoneal injection with a dose of 50 mg/kg for 14 days before injection of 50 mg/kg BrdU for 3 days and twice per day.The changes in body weight and behavioral activity was observed.Immunohistochemistry and BrdU labeling were used to investigate the effect on number of neural stem cells in the subgranular zone(SGZ).Influences of acrylamide on the expression of proliferation associated genes (JNK3,Akt1,Gsk-3β,RhoA and Rac1) were also examined using RT-PCR.【Result】Result showed that the body weight of acrylamide exposed mice was significantly lower than that of the control group.The mice in acrylamide exposed group were listless with weak hind limbs,which showed splitting position when walking.BrdU-positive cells in experimentally acrylamide exposed mice were extremely significantly decreased compared with that in the control group (P<0.01).JNK3 and Rac1 mRNA expressions were remarkably increased (P<0.05),while Akt1,Gsk-3β and RhoA mRNA expressions were very significantly increased (P<0.01).【Conclusion】Acrylamide poisoning suppressed the proliferation of adult neural stem cells of dentate gyrus in mouse and influenced the expression of JNK3,Akt1,Gsk-3β,Rac1 and RhoA in mouse hippocampus.
Key words:  acrylamide poisoning  adult neurogenesis  immunohistochemistry  proliferation-associated gene

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